Desenvolvimento de um nanogel de triancinolona acetonida com potencial aplicação no tratamento de úlceras orais traumáticas

Abstract

Traumatic oral ulcers (TOU) are lesions that occur in the mucosa of the outh, resulting from physical injuries. These lesions impair basic functions such as chewing, swallowing, and speaking, and usually take 10 to 14 days to heal. The usual treatment for oral TOU involves topical medications containing triamcinolone acetonide (TA). TA is a synthetic glucocorticoid with potent anti-inflammatory and immunosuppressive action, widely used in the treatment of inflammatory conditions of the oral cavity. However, conventional topical formulations of TA have significant limitations such as: low bioavailability, the need for multiple daily applications, unpleasant sensory experience in the mouth, and poor retention in the oral mucosa. Nanotechnology emerges as a promising alternative to overcome the physicochemical and biopharmaceutical aspects of drugs. Nanoemulsions (NEs) are thermodynamically stable mixtures of oil, water, and surfactants, with droplets in the nano scale.The incorporation of a gelling polymer into NE forms nanogels, which may exhibit mucoadhesive characteristics, promoting greater retention and sustained release of the drug at the lesion. Thus, the study aimed to develop and characterize physicochemically a chitosan nanogel containing triamcinolone acetonide (TA) with potential application in the treatment of traumatic oral ulcers. The main results demonstrated that glyceryl monooleate (Peceol®) and monoethanolamine dietheylene glycol ether (Transcutol®) were essential for the efficient solubilization of TA, resulting in homogeneous and stable nanoemulsions.The low-energy phase inversion emulsification technique proved to be effective, and the ideal stirring time was 6 hours to stabilize the physicochemical parameters. The obtained nanoemulsions had droplet sizes smaller than 250 nm and PDI below 0.3. The incorporation of the gelling polymers chitosan and Natrosol allowed for the creation of nanogels with mucoadhesive potential, which remained visually homogeneous and showed no signs of instability for 35 days. From the more stable nanoemulsion, nanogels were prepared with chitosan and Natrosol as gelling agents, evaluating different polymer ratios. The nanogels showed a homogeneous appearance, pH compatible with the oral mucosa (adjusted to 7.0), good stability, and potential topical application.The final formulation, containing TA in a mucoadhesive nanostructured system, proved to be promising for improving retention at the lesion site, favoring sustained drug release, and increasing therapeutic efficacy in the treatment of traumatic oral ulcers. In conclusion, the development of triamsinolone acetonide nanogel in this study represents a promising nanotechnological approach for the management of traumatic oral ulcers, overcoming the clinical hurdles of conventional formulations and advancing the development of more effective topical therapies with greater adherence.